Association of Amino Acid Substitution Pattern in Core Protein of Hepatitis C Virus Genotype 1b High Viral Load and Non-Virological Response to Interferon-Ribavirin Combination Therapy
Objective: Patients with high titer (≧100 kIU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve highly sustained virological response rates to combination therapy with interferon plus ribavirin. Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA neg...
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| Veröffentlicht in: | Intervirology 2005-01, Vol.48 (6), p.372-380 |
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| creator | Akuta, Norio Suzuki, Fumitaka Sezaki, Hitomi Suzuki, Yoshiyuki Hosaka, Tetsuya Someya, Takashi Kobayashi, Masahiro Saitoh, Satoshi Watahiki, Sachiyo Sato, Junko Matsuda, Marie Kobayashi, Mariko Arase, Yasuji Ikeda, Kenji Kumada, Hiromitsu |
| description | Objective: Patients with high titer (≧100 kIU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve highly sustained virological response rates to combination therapy with interferon plus ribavirin. Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs. Methods: We evaluated 50 consecutive Japanese adults with high titer of HCV genotype 1b who received combination therapy for 48 weeks. We investigated the pretreatment substitution patterns in amino acids 1–191 of the core region and amino acids 2209–2248 of NS5A, and early viral kinetics. Results: Overall, a non-virological response was noted in 12 (24%) patients. Multivariate analysis identified serum albumin |
| doi_str_mv | 10.1159/000086064 |
| format | Article |
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Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs. Methods: We evaluated 50 consecutive Japanese adults with high titer of HCV genotype 1b who received combination therapy for 48 weeks. We investigated the pretreatment substitution patterns in amino acids 1–191 of the core region and amino acids 2209–2248 of NS5A, and early viral kinetics. Results: Overall, a non-virological response was noted in 12 (24%) patients. Multivariate analysis identified serum albumin <3.9 g/dl, substitutions of amino acid 70 in the core region, and substitutions of amino acid 91 as independent and significant factors associated with a non-virological response. Especially, substitutions of arginine (R) by glutamine (Q) at amino acid 70, and/or leucine (L) by methionine (M) at amino acid 91 were significantly more common in NVRs. The falls in HCV-RNA levels during treatment in patients with specific substitutions in the core region were significantly less than in those without such substitutions. Conclusions: Our results suggest that serum albumin and amino acid substitution patterns in the core region in patients with high titers of HCV genotype 1b may have an effect on combination therapy in NVRs. Further large-scale studies are required to examine the role of amino acid substitutions specific to a non-virological response to combination therapy.</description><identifier>ISSN: 0300-5526</identifier><identifier>EISSN: 1423-0100</identifier><identifier>DOI: 10.1159/000086064</identifier><identifier>PMID: 16024941</identifier><identifier>CODEN: IVRYAK</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Adult ; Aged ; Amino Acid Sequence ; Amino Acid Substitution ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Drug Resistance, Viral ; Drug Therapy, Combination ; Female ; Hepacivirus - classification ; Hepacivirus - genetics ; Hepacivirus - physiology ; Hepatitis C - drug therapy ; Hepatitis C - virology ; Hepatitis C virus ; Humans ; Interferons - pharmacology ; Interferons - therapeutic use ; Japan ; Male ; Middle Aged ; Molecular Sequence Data ; Multivariate Analysis ; Original Paper ; Ribavirin - pharmacology ; Ribavirin - therapeutic use ; RNA, Viral - blood ; Serum Albumin - analysis ; Viral Core Proteins - chemistry ; Viral Core Proteins - genetics ; Viral Load ; Viral Nonstructural Proteins - chemistry ; Viral Nonstructural Proteins - genetics</subject><ispartof>Intervirology, 2005-01, Vol.48 (6), p.372-380</ispartof><rights>2005 S. Karger AG, Basel</rights><rights>Copyright (c) 2005 S. Karger AG, Basel.</rights><rights>Copyright (c) 2005 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-86b54eb8a95e7a5ab6282316a755154214bf647d29fce6830cb44c35ca28247e3</citedby><cites>FETCH-LOGICAL-c427t-86b54eb8a95e7a5ab6282316a755154214bf647d29fce6830cb44c35ca28247e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,2423,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16024941$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akuta, Norio</creatorcontrib><creatorcontrib>Suzuki, Fumitaka</creatorcontrib><creatorcontrib>Sezaki, Hitomi</creatorcontrib><creatorcontrib>Suzuki, Yoshiyuki</creatorcontrib><creatorcontrib>Hosaka, Tetsuya</creatorcontrib><creatorcontrib>Someya, Takashi</creatorcontrib><creatorcontrib>Kobayashi, Masahiro</creatorcontrib><creatorcontrib>Saitoh, Satoshi</creatorcontrib><creatorcontrib>Watahiki, Sachiyo</creatorcontrib><creatorcontrib>Sato, Junko</creatorcontrib><creatorcontrib>Matsuda, Marie</creatorcontrib><creatorcontrib>Kobayashi, Mariko</creatorcontrib><creatorcontrib>Arase, Yasuji</creatorcontrib><creatorcontrib>Ikeda, Kenji</creatorcontrib><creatorcontrib>Kumada, Hiromitsu</creatorcontrib><title>Association of Amino Acid Substitution Pattern in Core Protein of Hepatitis C Virus Genotype 1b High Viral Load and Non-Virological Response to Interferon-Ribavirin Combination Therapy</title><title>Intervirology</title><addtitle>Intervirology</addtitle><description>Objective: Patients with high titer (≧100 kIU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve highly sustained virological response rates to combination therapy with interferon plus ribavirin. Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs. Methods: We evaluated 50 consecutive Japanese adults with high titer of HCV genotype 1b who received combination therapy for 48 weeks. We investigated the pretreatment substitution patterns in amino acids 1–191 of the core region and amino acids 2209–2248 of NS5A, and early viral kinetics. Results: Overall, a non-virological response was noted in 12 (24%) patients. Multivariate analysis identified serum albumin <3.9 g/dl, substitutions of amino acid 70 in the core region, and substitutions of amino acid 91 as independent and significant factors associated with a non-virological response. Especially, substitutions of arginine (R) by glutamine (Q) at amino acid 70, and/or leucine (L) by methionine (M) at amino acid 91 were significantly more common in NVRs. The falls in HCV-RNA levels during treatment in patients with specific substitutions in the core region were significantly less than in those without such substitutions. Conclusions: Our results suggest that serum albumin and amino acid substitution patterns in the core region in patients with high titers of HCV genotype 1b may have an effect on combination therapy in NVRs. Further large-scale studies are required to examine the role of amino acid substitutions specific to a non-virological response to combination therapy.</description><subject>Adult</subject><subject>Aged</subject><subject>Amino Acid Sequence</subject><subject>Amino Acid Substitution</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Drug Resistance, Viral</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Hepacivirus - classification</subject><subject>Hepacivirus - genetics</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis C - drug therapy</subject><subject>Hepatitis C - virology</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>Interferons - pharmacology</subject><subject>Interferons - therapeutic use</subject><subject>Japan</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Multivariate Analysis</subject><subject>Original Paper</subject><subject>Ribavirin - pharmacology</subject><subject>Ribavirin - therapeutic use</subject><subject>RNA, Viral - blood</subject><subject>Serum Albumin - analysis</subject><subject>Viral Core Proteins - chemistry</subject><subject>Viral Core Proteins - genetics</subject><subject>Viral Load</subject><subject>Viral Nonstructural Proteins - chemistry</subject><subject>Viral Nonstructural Proteins - genetics</subject><issn>0300-5526</issn><issn>1423-0100</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpd0U9rFDEUAPAgil2rB8-CBA-Ch9Ekk2Rmj8ui3cLSltr2OiSZN9vUmWSaZIT9Zn48052lgrkE3vu9P_AQek_JV0rF8hvJr5ZE8hdoQTkrC0IJeYkWpCSkEILJE_QmxoesSlqS1-iESsL4ktMF-rOK0RurkvUO-w6vBus8Xhnb4p-Tjsmm6ZC6UilBcNg6vPYB8FXwCeyhZANjLk824jW-s2GK-AycT_sRMNV4Y3f3T2HV461XLVauxRfeFTnke7-zJieuIY7eRcDJ43OX53QQMrm2Wv224TBy0NbNS97cQ1Dj_i161ak-wrvjf4puf3y_WW-K7eXZ-Xq1LQxnVSpqqQUHXaulgEoJpSWrWUmlqoSggjPKdSd51bJlZ0DWJTGac1MKo7LjFZSn6PPcdwz-cYKYmsFGA32vHPgpNrRiTAjJM_z0H3zwU3B5t4YRTrnggmX0ZUYm-BgDdM0Y7KDCvqGkebpl83zLbD8eG056gPafPB4vgw8z-KXCDsIzmMv_AuCOowg</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Akuta, Norio</creator><creator>Suzuki, Fumitaka</creator><creator>Sezaki, Hitomi</creator><creator>Suzuki, Yoshiyuki</creator><creator>Hosaka, Tetsuya</creator><creator>Someya, Takashi</creator><creator>Kobayashi, Masahiro</creator><creator>Saitoh, Satoshi</creator><creator>Watahiki, Sachiyo</creator><creator>Sato, Junko</creator><creator>Matsuda, Marie</creator><creator>Kobayashi, Mariko</creator><creator>Arase, Yasuji</creator><creator>Ikeda, Kenji</creator><creator>Kumada, Hiromitsu</creator><general>S. 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Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs. Methods: We evaluated 50 consecutive Japanese adults with high titer of HCV genotype 1b who received combination therapy for 48 weeks. We investigated the pretreatment substitution patterns in amino acids 1–191 of the core region and amino acids 2209–2248 of NS5A, and early viral kinetics. Results: Overall, a non-virological response was noted in 12 (24%) patients. Multivariate analysis identified serum albumin <3.9 g/dl, substitutions of amino acid 70 in the core region, and substitutions of amino acid 91 as independent and significant factors associated with a non-virological response. Especially, substitutions of arginine (R) by glutamine (Q) at amino acid 70, and/or leucine (L) by methionine (M) at amino acid 91 were significantly more common in NVRs. The falls in HCV-RNA levels during treatment in patients with specific substitutions in the core region were significantly less than in those without such substitutions. Conclusions: Our results suggest that serum albumin and amino acid substitution patterns in the core region in patients with high titers of HCV genotype 1b may have an effect on combination therapy in NVRs. Further large-scale studies are required to examine the role of amino acid substitutions specific to a non-virological response to combination therapy.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>16024941</pmid><doi>10.1159/000086064</doi><tpages>9</tpages></addata></record> |
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| ispartof | Intervirology, 2005-01, Vol.48 (6), p.372-380 |
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| language | eng |
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| source | MEDLINE; Karger Journals |
| subjects | Adult Aged Amino Acid Sequence Amino Acid Substitution Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Drug Resistance, Viral Drug Therapy, Combination Female Hepacivirus - classification Hepacivirus - genetics Hepacivirus - physiology Hepatitis C - drug therapy Hepatitis C - virology Hepatitis C virus Humans Interferons - pharmacology Interferons - therapeutic use Japan Male Middle Aged Molecular Sequence Data Multivariate Analysis Original Paper Ribavirin - pharmacology Ribavirin - therapeutic use RNA, Viral - blood Serum Albumin - analysis Viral Core Proteins - chemistry Viral Core Proteins - genetics Viral Load Viral Nonstructural Proteins - chemistry Viral Nonstructural Proteins - genetics |
| title | Association of Amino Acid Substitution Pattern in Core Protein of Hepatitis C Virus Genotype 1b High Viral Load and Non-Virological Response to Interferon-Ribavirin Combination Therapy |
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